The reduction of prochiral ketones produces an alcohol which contains an asymmetric carbon atom, designated by the asterik in the following reaction. ##STR1## Considerable effort has been expended in the past and continues to be expended in finding asymmetric reducing agents which will achieve the reduction of such carbonyl groups to give optically active alcohols of high optical purity (100% optical purity=100% ee).
One valuable reagent is B-isopinocampheyl-9-borabicyclo[3.3.1]nonane, B-Ipc-9-BBN, made by hydroborating optically active .alpha.-pinene with 9-borabicyclo[3.3.1]nonane (9-BBN) and sold by Aldrich Chemical Company under the registered trademark Alpine-Borane, and the modified borohydride reagent, NB-Enantride [M. M. Midland, A. Kazubski, J. Org. Chem., 47, 2495 (1982). ##STR2##
This reagent readily reacts with deuteroaldehydes, RCDO, to give the reduced product, a primary alcohol, in optical purities approaching 100% [M. M. Midland, S. Greer, A. Tramontano, S. A. Zderic, J. A. Chem. Soc., 47, 2352 (1979)]. ##STR3##
The .alpha.-pinene can be recovered and reused.
Originally, this reagent gave very poor results in the reduction of ketones. [A. Tramontano, Ph.D. Thesis, U. Cal. Riverside, (1980)], resulting in end product of only 7% optical purity. ##STR4##
However, it does reduce acetylenic ketones in high optical purity [M. M. Midland, A. Tramontano, A. Kazubski, R. S. Graham, D. S. Tsai, D. B. Cardin, Tetrahedron, 40, 1371 (1984)]. ##STR5##
Another modified borohydride reagent, K 9-O-DIPGF-9-BBNH is highly promising. [H. C. Brown, W. S. Park and B. T. Cho, J. Org. Chem., 51, 0000 (1986)].
In addition, an enzymatic chiral reduction of ketones was recently reported by E. Keinan, E. K. Hafeli, K. K. Seth and R. Lamed, J. Am. Chem. Soc., 108, 162 (1986).
It still remains highly desirable to find a reagent that will do equally well in reducing aliphatic, alicyclic, and aromatic ketones. Indeed, it was discovered that carrying out the reaction under neat conditions or concentrated solutions provided product having 87% optical purity. [H. C. Brown and G. G. Pai, J. Org. Chem., 50, 1384 (1985)]. ##STR6##
Even better results (94% optical purity) can be realized by carrying out the reduction under exceptionally high pressures, 6000 atmos. [M. M. Midland and J. I. McLoughlin, J. Org. Chem., 49, 1317 (1984)]. ##STR7##
Nevertheless, there remains a longstanding need for reagents which have an exceptional ability to achieve the reduction of many types of ketones in very high optical purities under very simple conditions. The present invention provides such reagents.